We propose to perform further epidemiological analyses of data collected in a previous study of oxidative damage in humans. We conducted a randomized intervention trial of smokers and passive smokers, with measurement of two biomarkers of lipid peroxidation (malondialdehyde, MDA; and F2-isoprostanes, Iso-P). Laboratory data support a relationship between oxidative damage and cancer, and epidemiological studies have shown an inverse association between consumption of fruit and vegetables or specific antioxidants and risk of some cancers. Demonstration of a causal relationship will require evidence that anti-oxidant treatment can decrease oxidative damage, and ultimately that decreasing oxidative damage will reduce disease. Our study will provide information needed by other researchers to study oxidative damage and antioxidants in cancer prevention. 325 Subjects were recruited (142 smokers, 81 passive smokers and 102 non-smokers), 750 clinic visits conducted, 3700 vacutainers of blood collected and 10,000 vials of plasma frozen. After two baseline visits, smokers and passive smokers were randomized to either placebo, vitamin C or an anti-oxidant cocktail. All assays have been completed, including MDA, Iso-P, vitamins C, E, A carotenoids, lipids, C-reactive protein and continine. We have already completed statistical of the effect of anti-oxidant supplementation on Iso-P in smokers, the effect of smoking status on the level of several anti-oxidants in the blood, and predictors of lipid peroxidation. We are seeking funding to carry out further statistical analyses of these data. SPECIFIC AIMS 1) To determine effects of antioxidant treatment on F2-isoprostanes in passive smokers 2) To determine effects of anti-oxidant treatment on MDA in both smokers and passive smokers 3) To determine effects of antioxidant treatment on C-reactive protein in both smokers and passive smokers 4) To estimate the intra-individual variability of oxidative damage, of plasma anti-oxidants and of plasma continue 5) To establish the predictors of C-reactive protein in smokers, non- smokers and passive smokers 6) To determine the level of vitamin C required by smokers to attain the plasma vitamin C levels of non-smokers 7) To study the effect of supplemental vitamin C or antioxidant cocktail on other plasma antioxidants